PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease

BMC Molecular and Cell Biology

article

Thejer, Bashar M.¹  Ludescher, Marina³  Gray, Lesley-Ann⁴  Pawlak, Michael⁵  Wallace, Robyn H.¹  Pant, Sameer D.⁶  Wong, Marie⁷  Fischer, Tamas⁸  New, Elizabeth J.⁹  Fehm, Tanja N.³  Neubauer, Hans³  Adhikary, Partho P.¹  Goldys, Ewa M.^1,11  Quinn, Jane C.^1,13  Weston, Leslie A.^1,13  Cahill, Michael A.¹  Teakel, Sarah L.¹  Fang, Johnny¹  Weston, Paul A.^1,13  Gurusinghe, Saliya^1,13  Anwer, Ayad G.^1,11  Gosnell, Martin^1,11  Jazayeri, Jalal A.¹ 

[1] School of Biomedical Sciences, Charles Sturt University;Department of Biology, College of Science, University of Wasit;Department of Gynecology and Obstetrics, University Women’s Hospital of Dusseldorf;Australian Genome Research Facility Ltd., Victorian Comprehensive Cancer Centre;NMI TT Pharmaservices;School of Animal and Veterinary Sciences, Charles Sturt University;Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research;ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Australian National University;University of Sydney, School of Chemistry;Present Address: Faculty of Pharmaceutical Sciences, The University of British Columbia;ARC Centre of Excellence for Nanoscale BioPhotonics, Macquarie University;Present Address: The Graduate School of Biomedical Engineering, University of New South Wales;Graham Centre for Agricultural Innovation, Charles Sturt University;Faculty of Science, Charles Sturt University;School of Agricultural and Wine Sciences, Charles Sturt University;Quantitative (Biotechnology) Pty. Ltd.

关键词: Epigenetics;    Genomic sequence;    Hyperspectral autofluorescence;    Organizer;    Embryology;    Metabolism;    Cell death;    Cytochrome P450;    Steroid biology;   

DOI  :  10.1186/s12860-020-00268-z

学科分类：内科医学

来源: Colegio Oficial de Psicologos

【 摘 要 】

Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation. Here, we show that mutagenic manipulation of PGRMC1 phosphorylation alters cell metabolism, genomic stability, and CpG methylation. Each of several mutants elicited distinct patterns of genomic CpG methylation. Mutation of S57A/Y180/S181A led to increased net hypermethylation, reminiscent of embryonic stem cells. Pathways enrichment analysis suggested modulation of processes related to animal cell differentiation status and tissue identity, as well as cell cycle control and ATM/ATR DNA damage repair regulation. We detected different genomic mutation rates in culture. A companion manuscript shows that these cell states dramatically affect protein abundances, cell and mitochondrial morphology, and glycolytic metabolism. We propose that PGRMC1 phosphorylation status modulates cellular plasticity mechanisms relevant to early embryological tissue differentiation.

【 授权许可】

CC BY|CC0